Effect of nicotinamide analogues on recovery from DNA damage in C3H10T1/2 cells.

The effects of nicotinamide analogues on cellular recovery following N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment have been characterized in the transformable cell line, C3H10T1/2. The recovery of cell division potential was measured under conditions which allow simultaneous quantification of intracellular levels of poly(adenosine diphosphate ribose), nicotinamide adenine dinucleotide, and rates of RNA, DNA, and protein synthesis. 3- Methoxybenzamide (MBA), 3-aminobenzamide, and benzamide, which are effective inhibitors of adenosine diphosphate ribosyltransferases , blocked recovery of cell division following treatment with 34 microM MNNG, while the noninhibitors , 3- methoxybenzoate and benzoate, had no effect. In the presence of MBA, cells progressively lost the ability to resume cell division during the first 24 to 36 hr following DNA damage. The intracellular levels of poly(adenosine diphosphate ribose) increased approximately 7-fold within 20 min following MNNG treatment, and 1 mM MBA inhibited this increase by approximately 82%. In the presence of MBA, a dramatic decrease in the rate of DNA synthesis occurred approximately 16 hr after MNNG treatment, while RNA and protein synthesis continued at rates similar to those in cells treated with MNNG alone.